Allogeneic Blood Stem Cell Transplantation and Adoptive Immunotherapy for Hodgkin's Disease - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00385788

Purpose

The goal of this clinical research study is to learn if fludarabine, melphalan and gemcitabine followed by transplantation of stem cells (blood-forming cells) as well as immune cells (lymphocytes), collected from a matched related (i.e. a sibling) or unrelated donor, or a mismatched related donor, can help to control Hodgkin's disease. The safety of the treatment will also be studied.

Condition	Intervention	Phase
Hodgkin's Disease	Drug: Gemcitabine Drug: Fludarabine Drug: Melphalan Drug: Antithymocyte Globulin Procedure: Allogeneic Stem Cell Infusion	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Allogeneic Stem Cell Transplantation Followed By Adoptive Immunotherapy for Patients With Relapsed and Refractory Hodgkin's Disease

Resource links provided by NLM:

MedlinePlus related topics: Cancer Hodgkin Disease

Drug Information available for: Fludarabine Fludarabine monophosphate Gemcitabine Gemcitabine hydrochloride Melphalan Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Transplant Related Mortality [ Time Frame: Transplant to 100 days post transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	July 2005
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Gemcitabine + Fludarabine + Melphalan	Drug: Gemcitabine 800 mg/m^2 IV Over 30 Minutes x 1 Day Other Names: Gemzar Gemcitabine hydrochloride Drug: Fludarabine 33 mg/m^2 IV Over 30 Minutes x 4 Days Other Names: Fludarabine Phosphate Fludara Drug: Melphalan 70 mg/m^2 IV Over 30 Minutes x 2 Days Drug: Antithymocyte Globulin 2 mg/kg IV for two days before stem cell transplantation. If you are receiving a transplant from a matched unrelated donor (not a blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant. Other Names: ATG Thymoglobulin Procedure: Allogeneic Stem Cell Infusion Infusion of stem cells on Day 0. Other Names: AST Stem Cell Transplantation SCT

Arms

Assigned Interventions

Experimental: Gemcitabine + Fludarabine + Melphalan

Drug: Gemcitabine

800 mg/m^2 IV Over 30 Minutes x 1 Day

Other Names:

Gemzar
Gemcitabine hydrochloride

Drug: Fludarabine

33 mg/m^2 IV Over 30 Minutes x 4 Days

Other Names:

Fludarabine Phosphate
Fludara

Drug: Melphalan

70 mg/m^2 IV Over 30 Minutes x 2 Days

Drug: Antithymocyte Globulin

2 mg/kg IV for two days before stem cell transplantation.

If you are receiving a transplant from a matched unrelated donor (not a blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant.

Other Names:

ATG
Thymoglobulin

Procedure: Allogeneic Stem Cell Infusion

Infusion of stem cells on Day 0.

Other Names:

AST
Stem Cell Transplantation
SCT

Detailed Description:

The main drugs used in this study are fludarabine, melphalan and gemcitabine. Fludarabine is a drug designed to weaken the immune defenses in order to allow the body to accept donors' cells. Melphalan is a chemotherapy drug that weakens the immune system but also kills cancer cells present in the body. Gemcitabine is a chemotherapy drug that kills cancer cells present in the body.

If you are found to be eligible to take part in this study, you will have a plastic tube (catheter) inserted into a vein under the collarbone. Drugs, blood products, and stem cells will be given and taken through this tube.

Gemcitabine will be given by vein or through the catheter for one day. Fludarabine will be given through the catheter once a day for 4 days. You will also receive melphalan once daily for 2 days. If you are receiving a transplant from a matched unrelated donor (not a blood relative), a mismatched related donor (a blood relative, but not a full match), you will also receive antithymocyte globulin (ATG) once a day for 2 days. ATG is given to decrease the risk of graft-versus-host disease. Tacrolimus will also be given to all patients to decrease the risk of (or treat) graft-versus-host disease. All participants are expected to need blood transfusions as part of this treatment.

Beginning 2 days before the transplant, tacrolimus will be given through the catheter over 24 hours. This will be changed to pills once you can tolerate swallowing pills. If no active cancer is detected and there is no graft-versus-host disease, you will then swallow 1 or more tacrolimus pills a day for only about 3-4 months, instead of the usual period of 6 months. This is done to boost the donor immune system against the cancer.

On the transplant day ("Day 0"), the stem cells or bone marrow collected from the donor will be infused through the catheter ("transplant"). You will receive a mixture of stem cells and immune cells. Drugs such as corticosteroids, acetaminophen (Tylenol), and/or Benadryl will be given through the catheter, before the infusion, to decrease the chance of allergic reactions. Starting on Day 7 after the transplant, filgrastim (G-CSF) will be given as an injection under the skin or through a needle to increase the growth of white blood cells. Methotrexate, a chemotherapy drug, will be given in small doses through the catheter on Days 1,3,6, 11 after the transplant to decrease the risk of graft-versus-host disease (GVHD).

If you have persistent but stable (not "growing") disease after transplant, you will have your immunosuppressive medications (tacrolimus, corticosteroids) stopped even before 4 months. If there is no response, you will receive an infusion of additional cells from your donor. If you have progressive ("growing") Hodgkin's disease after the transplant, you will be taken off study, and other treatment options may be explored.

Blood, bone marrow, and x-ray examinations will be performed periodically to monitor the results of the bone marrow transplantation. Blood tests will usually require up to 3-4 tablespoons of blood. These examinations will be done before the transplant, before you are released to go back home (about 100 days after the transplant), and then as deemed necessary by your physician. Blood tests will be done daily while you are hospitalized and several times a week until your blood counts recover.

This is an investigational study. All of the drugs used in this study are FDA-approved and commercially available. Up to 50 patients will take part in this study. All will be enrolled at MD Anderson.

Eligibility

Ages Eligible for Study:	up to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients < 65 years of age with histologically confirmed refractory or relapsed Hodgkin's disease (including patients who fail or relapse after autologous SCT). In the event of transplants from unrelated donors, the upper age limit will be 50 years. Patients should have any of the following disease status: a. responsive or stable disease on salvage chemotherapy or radiation therapy. b. untreated, smoldering (i.e. not rapidly progressive) relapses.
Patients must have a serum bilirubin equal to or <2.0 mg/dl (isolated hyperbilirubinemia related to Gilbert's disease allowed), serum transaminase (ALT) equal to or < 3 times the upper limit of the normal range, serum creatinine <2.0 mg/dl (provided they also have a glomerular filtration rate of at least 55 ml/min), no symptomatic cardiac or pulmonary disease and a performance status equal to or <2. Left ventricular ejection fraction > or equal to 40%, FEV1, FVC and DLCO > or equal to 50% predicted .
Patients must have an HLA-compatible related or unrelated donor (one-antigen mismatched related donors are acceptable) willing to donate marrow or rhG-CSF-mobilized peripheral blood stem cells. In the event of transplants from matched unrelated donors, a high-resolution allele match for HLA-A, -B, -C, -DRB1 and DQB1 ("10 of 10 match") is required.
Women of childbearing potential must have a negative serum pregnancy test within two weeks of study entry and should be advised to avoid becoming pregnant. Men should be advised to not father a child while on treatment. Both women of childbearing potential and men must agree to practice effective methods of contraception.
Patients must be capable and willing to sign informed consent.

Exclusion Criteria:

Patients with documented disease progression on salvage chemotherapy.
Nursing or pregnant females. Should a woman become pregnant or suspect she is pregnant while participating in the study, she should inform her treating physician immediately.
Severe concomitant medical or psychiatric illness.
Uncontrolled arrhythmia or symptomatic cardiac or pulmonary disease.
Chronic active hepatitis or cirrhosis.
Active or uncontrolled infection.
Radiation therapy within 10 weeks of transplant admission. Radiation therapy shortly before the start of the preparative regimen is allowed.
Prior or concurrent malignancies (including myelodysplasia) except resected basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Protocol Chair. Cancer treated with curative intent > 5 years previously will be allowed.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00385788

Contacts

Contact: Paolo Anderlini, MD

713-792-8750

Locations

United States, Texas
UT MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Paolo Anderlini, MD

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Paolo Anderlini, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00385788 History of Changes
Other Study ID Numbers:	2005-0015
Study First Received:	October 9, 2006
Last Updated:	February 2, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Hodgkin's Disease
Stem Cell Transplantation
Antithymocyte Globulin
Gemcitabine
Gemzar
Fludarabine
Fludarabine Phosphate

Melphalan
Allogeneic stem cell transplantation
AST
SCT
ATG
Thymoglobulin

Additional relevant MeSH terms:

Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antilymphocyte Serum
Melphalan
Gemcitabine
Fludarabine monophosphate
Fludarabine
Vidarabine
Immunosuppressive Agents

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Myeloablative Agonists
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on February 09, 2012